Signal recognition particles (SRPs) are involved in synthesis of secretory protein in animal cells. SRP has a sedimentation coefficient of 11S as a whole and consists of 7SL RNA and 6 kinds of proteins.
Synthesis of secretory protein is initiated by binding of its mRNA to a free ribosome. The ribosome is a place for protein synthesis and consists of a rRNA and a large number of ribosomal proteins. In the case of eucaryotes, the ribosome has a sedimentation coefficient of 80S as a whole, and is further divided into 2 particles having sedimentation coefficients of 60S and 40S respectively, and the former has one molecule each of 5S, 5.8S and 28S rRNAs and the latter has one molecule of 18S rRNA.
SRP recognizes a signal peptide consisting of a hydrophobic amino acid sequence present in the N-terminal or in the vicinity of the N-terminal of a secretory protein precursor extended from the ribosome, and binds to a protein/ribosome complex. Succeeding translation of the protein is thereby terminated. SRP transports the complex to a membrane of an endoplasmic reticulum and binds to an SRP receptor protein present in the cytosol side of the endoplasmic reticulum. When the SRP-bound complex binds to the membrane, inhibition of the translation is canceled, thereby dissociating SRP to fix the ribosome to the membrane. Then, the translation is continued to allow a polypeptide chain to pass through the membrane to produce a mature secretory protein.
On the other hand, in the nucleus of the eucaryotic cell, not only mRNA and the like involved in translation of a protein as described above but also a group of RNAs called small nuclear RNAs of about 100 to 300 bases in length are synthesized. Usually, these bind to proteins and occur as ribonucleic proteins. For example, RNAs called U1, U2, U3, U4, U5 or U6 are known as the small nuclear RNAs. With respect to functions of the small nuclear RNAs, it has been revealed that U1, U2, U4, U5 and U6 participate in splicing of mRNA precursors, but other functions have not been well known yet.
Although there are thus many unrevealed features with respect to the functions of the small nuclear RNAs, it has been reported that U5 RNA cancerates cultured cells by transfection (see Non-Patent Publication 1). It has also been revealed that a transcript (transforming RNA) having poly(A) added to a nucleotide sequence (SEQ ID NO: 2) at the 3′-terminal side of a first stem in a secondary structure of U5 RNA, which was transcribed in a way dependent on RNA polymerase II, also similarly has a canceration ability (see Non-Patent Publication 2). This canceration ability was dependent on a specific nucleotide sequence (SEQ ID NO: 3) in the transforming RNA.
In a protein synthesis experiment using a rabbit reticulocyte extract, the transforming RNA suppressed synthesis of a secretory protein (see Non-Patent Publication 3). An oligodeoxynucleotide (ODN) having a nucleotide sequence set forth in SEQ ID NO: 4 also suppressed synthesis of a secretory protein in the rabbit reticulocyte extract. Furthermore, it was revealed that a specific part of nucleotide sequence (SEQ ID NO: 5) in the ODN binds to ribosomal 28S RNA. On the other hand, it was reported that an antisense oligodeoxynucleotide (antisense ODN; SEQ ID NO: 6) of the ODN binds to 7SL RNA in SRP and works for lowering suppression of secretory protein synthesis (resulting in enhancement of secretory protein synthesis), and also that a specific part of nucleotide sequence (SEQ ID NO: 7) in the antisense ODN binds to a nucleotide sequence (SEQ ID NO: 8) of positions 48 to 51 of 7SL RNA (see FIG. 1).
These reports suggest that the nucleotide sequence present in U5 RNA exhibits a canceration ability and an ability to suppress synthesis of a secretory protein as new functions, and simultaneously the antisense ODN to the part of nucleotide sequence presumed to participate in exhibition of the canceration ability and the like of U5 RNA has an action of suppressing the canceration ability and the like of U5 RNA, but which element is necessary and sufficient for suppression of the canceration ability and the like of U5 RNA is still unrevealed.    Non-Patent Publication 1: Mol. Cell. Biol., 9, 4345-4356 (1989)    Non-Patent Publication 2: Mol. Carcinog. 20, 175-188 (1997)    Non-Patent Publication 3: J. Biol. Chem. 274(22), 15786-15796 (1999)